Youssef El-Arabi scored in the last minute of extra-time as Olympiakos knocked Arsenal out of the Europa League on Thursday on a night when four former European champions were eliminated.
Ajax, Celtic, Benfica and Porto went out but Manchester United hardly broke sweat after Simon Deli of Brugge conceded a penalty and earned a red card in the 23rd minute at Old Trafford.
Arsenal, last year's losing finalists, had won the first leg of the round of 32 tie 1-0 in Greece.
Defender Pape Abou Cisse cancelled out that advantage when he headed in a corner after 53 minutes.
Arsenal could not break through and were forced to extra time.
Pierre-Emerick Aubameyang put them back in front with a spectacular flying kick.
However, in the final minute of extra time, Arsenal cleared an Olympiakos corner but were still disorganised when the ball was swung back into the area.
The cross found El Arabi free in front of goal for an unchallenged shot.
"Very hard, very tough," said Aubameyang. "Their last-minute goal was unlucky for us."
At Old Trafford, Bruno Fernandes gave United the lead with a penalty after Deli's flying save.
Odion Ighalo, making his first start, hit his first goal for the club in the 34th minute.
- Tentative Ajax -
For the Nigerian, who says United were his childhood club, it was a moment to celebrate, but the emotion was mixed.
Ighalo lifted his shirt to reveal a picture of his sister Mary Atole who died suddenly at her home in Canada in December. Ighalo also has her name stitched into his boots.
Scott McTominay and Fred, with two late goals, completed the rout.
Ajax, Champions League semi-finalists last year, kicked off two goals down to Getafe, this season's Liga surprise team, and conceded another after five minutes.
Jaime Mata exploited tentative Ajax defending to spin and drill in a low shot from close range.
That left the home needed needing to score four, they managed two, the first from young Brazilian Danilo Pereira, with his first for the club, and an own goal when Mathias Olivera deflected a free kick. Getafe held on comfortably.
Copenhagen scored three goals on three shots as they won 3-1 at Celtic, but deserved the victory.
Jozo Simunovic's weak back pass gave Copenhagen the ball close to goal after 51 minutes and Micheal Santos completed the punishment.
With seven minutes left, Odsonne Edouard levelled with a penalty but as Celtic tried to press, their defence panicked twice in the last five minutes. Pep Biel and Dame N'Doye coolly accepted the gifts to make the aggregate score 4-2.
"It just wasn't our day and we're big boys, we can take it on the chin and we've got to make sure we bounce back," said Celtic captain Craig Brown
Benfica went out 5-4 on a aggregate after repeatedly throwing away the initiative as they drew 3-3 at home to Romanians Cluj.
Porto subsided 3-1 at home to Bayer Leverkusen to go out 5-2 overall.
The game between FC Salzburg and Eintracht Frankfurt was postponed because of a forecast of dangerously high winds and will be played on Friday.